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Biomedical subjects

L E McCoy

Publications and source records attributed to L E McCoy.

At least 19 recordsLinked to original sources

Treatment of cerebral ischemia with Dextran-40 or Fluosol DA 20%.

A cat stroke model was used to evaluate the efficacy of Dextran-40 (DEX) or Fluosol-DA 20% (FDA) in the treatment of focal cerebral ischemia. The animals were assigned randomly to one of three treatment groups: control, isovolemic hemodilution with DEX or isovolemic hemodilution with FDA. The oxidation state of cytochrome aa3 was measured in-vivo using near infrared reflectance spectrophotometry. The cerebral edema was measured by magnetic resonance imaging (MRI). The MRI edema indices for the three groups revealed that the FDA group had less edema (p less than 0.05), approaching that of non-stroke controls. The relative oxidation state of aa3 for the DEX group declined both during and after hemodilution. At the ninth hour post stroke the FDA group was better (aa3 more oxidized. p less than 0.025). Changes in blood and plasma components were reflective of the extent of hemodilution. Whole blood viscosity analysis revealed a difference (p less than 0.05) at the lower shear rates comparing DEX to FDA with FDA being higher than DEX. Two animals in each of the groups were allowed to awaken at the end of the procedure for functional assessment. These observations suggest that hemodilution with FDA following stroke significantly reduces early post-ischemic cerebral edema, improves oxidation in the peri-infarct area and appears to minimize functional deficits.

Animals↗

Acute severe carbon monoxide exposure in the rat: effects of hyperglycemia and hypoglycemia on mortality, recovery, and neurologic deficit.

Human and animal studies suggest a poorer outcome in the presence of abnormal blood glucose concentration during cerebral hypoxia-ischemia. It is unknown whether this is also the case in acute severe carbon monoxide poisoning. Using Levine-prepared rats, three groups were established and exposed to CO to answer this question: (1) hyperglycemics resulting from the administration of a 50% glucose solution, (2) hypoglycemics resulting from the administration of normal saline, and (3) untreated controls. The rats inhaled 2400 ppm CO for 90 min in the absence of anesthesia. Blood glucose was raised to a mean value of 402 mg/dL just prior to CO exposure in group 1. This resulted in an increased mortality rate (i.e., 54%), and during 4 h of room air recovery an impaired ability to regain body temperature, an increased plasma lactate dehydrogenase activity, and an increased neurologic deficit as compared with group 3. Hypoglycemia, which developed during CO exposure in group 2 (mean minimum glucose after 90 min, 44 mg/dL), resulted in an increased mortality rate (i.e., 46%), and during 4 h of room air recovery an impaired ability to regain body temperature and an increased neurologic deficit as compared with group 3. Blood glucose concentration in the rats in groups 2 and 3 that died during or shortly after CO exposure was significantly depressed relative to the survivors of those groups. Plasma insulin activity was elevated during CO exposure in group 1 as compared with group 3, but fell during recovery; insulin remained low throughout CO exposure and recovery in group 2. The results demonstrate the deleterious effects of both a very high and a very low blood glucose concentration during acute CO exposure.

Animals↗

MRI quantitation of edema in focal cerebral ischemia in cats: correlation with cytochrome aa3 oxidation state.

1H MRI permits detection of edema in the brain. In a middle cerebral artery stroke model in the cat, we found a significant correlation between an edema index based on MRI and a sensitive metabolic index of ischemia, the in vivo oxidation status of mitochondrial cytochrome aa3 determined by near-infrared reflectance spectrophotometry (r = -0.70, alpha = 0.001). This result suggests that a simple, noninvasive study using MRI can provide an index of the extent of ischemic damage in an experimental acute stroke model.

Animals↗

Role of Fluosol-DA 20% in prehospital resuscitation.

Fluosol-DA 20% (FDA-20) resuscitation has been proposed for prehospital therapy of hemorrhagic shock (HS). Acute HS (mean arterial pressure 60 mm Hg X 90 min, then 40 mm Hg X 30 min) in 24 splenectomized dogs was treated with 50 ml/kg of lactated Ringer's solution (RL) plus a volume equal to 105% of shed blood volume of FDA-20 (group 1), FDA-20 carrier Annex solution (group 2), or RL (group 3). Cardiopulmonary, hemopoietic, hemodynamic, and organ function parameters were measured preshock, at the end of shock, and at 30 and 60 min, and 24 h after resuscitation. FDA-20 produced effective volume expansion, oxygen delivery, and oxygen consumption. The FDA-20 appeared to affect organ function and cells adversely as reflected by a fall in red cell mass and platelet levels and by a rise in liver enzymes, BUN, and serum creatinine. Both the FDA-20 and Annex solution led to a reduction in serum proteins including serum albumin, serum globulin, immunoglobulin-G, and fibrinogen. These reductions are probably due to an oncotically driven factor which appears to maintain an optimal lymph to plasma oncotic ratio. The hydroxyethyl starch in the FDA-20 and the Annex solution, thus, would drive the plasma proteins into the interstitial space. The prolonged prothrombin times and the activated partial thromboplastin times after FDA-20 may be due, in part, to a reduction in the coagulation proteins, although these were not measured. Pending further studies designed to assess the effects of FDA-20 on possible cellular and multiple organ toxicity, clinical studies are premature and unwarranted.

Animals↗

Regenerative responses to exchange perfusion.

Isovolemic exchange perfusion of conscious normal and splenectomized rats to a Hct of +/- 3% with the perfluorocarbon based oxygen transport fluid, Fluosol-DA 20%, is characterized by: 1) a greater than projected depression of fibrinogen and the plasma globulins and 2) a rapid regeneration of these and certain other plasma proteins. Similar responses were observed in a study of PFC resuscitation of hemorrhagic shock in splenectomized dogs in which there was a selective depression of the platelets, the plasma globulins, IgG and fibrinogen. In the rats, the red cells and platelets required 14-21 days to return to control levels while the leukocytes returned to normal in 1-2 days. The globulins and fibrinogen exhibited a transient rebound response at 3 and 12 hours post exchange respectively with total protein levels restored to control levels at 48 hours. In the shock study, the leukocytes, which remained at control levels throughout the shock period and for 1 hour post resuscitation were 2.5x control levels at 24 hours. The platelets which were depressed to 20% of control levels following resuscitation remained depressed through the 24 hour time course of the study. Implicit in these results is the possibility that; A) thrombosis and B) immunosuppression may be caused by some component(s) of the perfusion/resuscitation fluid.

Animals↗

Endothelial response to perfluorochemical perfusion.

The purpose of this study was to evaluate, in vivo, the effect of perfluorochemical (PFC) blood substitutes on arterial endothelium following total blood replacement. Conscious-female-Sprague-Dawley rats (150-200 gms) were isovolumically exchange perfused with 3 blood volumes of PFC emulsion in an oxygen chamber. The exchange was performed at 0.5 ml/min via an indwelling-intracardiac-double-lumen catheter. One hour after the exchange, the animal was sacrificed and the circulatory system flushed free of blood and PFC emulsion with Dulbecco's solution, followed by perfusion fixation with glutaraldehyde solution. The heart, lungs and thoracic aorta were excised. The pulmonary arterial endothelial cell response was determined by scanning electron microscopy (SEM) following acute exposure to PFC emulsions under conditions of varied pH, oncotic pressure and emulsion age. These endothelial surfaces exhibited increased microvilli, leukocyte adhesion, fibrin deposition and subendothelium exposure. The magnitude of these abnormal responses varied with the degree of alkalinity and reduced oncotic pressure of the perfusate.

Animals↗

A method for evaluation of blood substitutes in the conscious animal.

Physiological evaluation of new and potential blood replacement agents has not kept pace with the development of such agents. Current procedures involve partial or total blood replacement in the anesthetized animal. This introduces the variable of anesthesia and eliminates the ability to observe behavior changes during blood replacement. Clinically, many patients receive blood or will receive artificial agents while sedated or under anesthesia, whereas others will be conscious. It is essential that evaluative studies be performed on the awake animal using procedures that are nontraumatic and nonrestrictive. A technique for isovolumic exchange perfusion utilizing an indwelling, heparin-coated, double-lumen catheter in the right atrium of a conscious rat is described. This animal model system permits continuous pre- and postperfusion monitoring. Nearly total blood replacement with perfluorochemical blood substitutes causes no discerniable discomfort or adverse reactions in the animal. Such animals thrive and replace missing hematologic components in 1-3 wk. The technique described can, with minimal modification, be used for isovolumic exchange perfusion of larger animals.

Animals↗

Purification and characterization of human and bovine platelet factor 4.

Platelet antiheparin, platelet factor 4, was isolated from freeze-thaw lysates of fresh bovine and outdated human platelet concentrates by a single step affinity chromatographic procedure. The yields of PF4 were 93 microgram and 142 microgram/ml of human and bovine platelets respectively. Antiheparin activity of the products were 558 units/mg for the bovine isolate and 489 units/mg for the human material. The bovine product is a single chain polypeptide with an apparent molecular weight of 12,300. Amino acid composition indicates 107-109 residues compared to the smaller human product which has an apparent molecular weight of 8,000 for a 70 residue polypeptide. The intact polypeptide was resistant to enzymatic hydrolysis as opposed to the reduced-alkylated derivative which was susceptible to hydrolysis in the presence and absence of heparin.

Amino Acids↗